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Safety and Efficacy Study of Concomitant Radiotherapy and Zoledronic Acid for Bone Metastases Palliation

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ClinicalTrials.gov Identifier: NCT00264420
Recruitment Status : Completed
First Posted : December 12, 2005
Last Update Posted : December 21, 2010
Information provided by:
The Cleveland Clinic

Brief Summary:
Zoledronic acid (Zometa) belongs to a class of drugs called bisphosphonates. Bisphosphonates are used in bone metastases to keep the cancerous lesion under control in the bone and to help prevent calcium level elevations in the blood. Cancer cell-culture studies at the Cleveland Clinic showed that zoledronic acid and radiation together have more cell killing effect than either one used alone. The purpose of this study is to monitor the healing of bone lesions when using zoledronic acid together with radiation treatment.

Condition or disease Intervention/treatment Phase
Bone Metastases Breast Cancer Lung Cancer Prostate Cancer Drug: zoledronic acid Phase 1

Detailed Description:

Bone metastases are frequently one of the first signs of disseminated disease in cancer patients. Skeletal complications due to metastatic disease include (severe) bone pain, impaired mobility, spinal cord compression, pathological fractures, and hypercalcemia. Radiotherapy and surgery are the options for the specific local treatment of bone metastases. Chemotherapy, hormonotherapy and bisphosphonates are systemic weapons used in the treatment of bone metastases with or without hypercalcemia. Cancers with propensity to metastasize to bones such as breast, prostate, lung and myeloma may possess the capacity to interact with osteoclasts. Osteoclasts are specialized bone cells, which erode mineralized bone by secreting acids and lysosomal enzymes. In normal bone remodeling, osteoclastic bone resorption is coupled to and is in equilibrium with osteoblastic bone formation. The lytic bone destruction associated with malignant bone metastases develops because tumor cells synthesize and release soluble factors that stimulate osteoclasts to resorb bone. The malignant activation of osteoclasts results in a disruption of normal bone remodeling wherein the equilibrium between bone resorption and bone formation is shifted toward increased bone resorption. This relative increase in osteoclastic bone resorption results in a net loss of bone.

Zoledronic acid (Zometa®, CGP42446) is a member of a class of compounds known as bisphosphonates. Bisphosphonates are effective inhibitors of osteoclastic bone resorption. They have therapeutic efficacy in the treatments of hypercalcemia of malignancy, lytic bone disease associated with multiple myeloma, and mixed lytic and blastic bone metastases associated with breast cancer, prostate cancer and lung cancer. In the clinical setting, zoledronic acid is the most potent bisphosphonate.

Conventionally, external beam radiotherapy (RT) is a primary treatment method for the palliation of bone metastases. The aim of RT in bone metastases treatment is to eradicate malignant cells without damaging surrounding normal cells. RT is typically given to the lesion area, in order to spare as much bone marrow as possible. RT is indicated in solitary, lytic and painful bone lesions of multiple myeloma as well as bone metastases from solid tumors such as breast, prostate and lung cancer to prevent the fracture risk or to relieve the pain.

The goal of this study will be to evaluate the safety and efficacy of concomitant standard RT and standard zoledronic acid on the bone metastases of breast, prostate or lung cancer patients. We chose zoledronic acid to use in this study, as it is the most effective FDA approved aminobisphosphonate.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Pilot Trial to Study the Safety and Efficacy of Concomitant Radiotherapy and Zoledronic Acid for the Palliation of Bone Metastases From Breast Cancer, Prostate Cancer and Lung Cancer
Study Start Date : December 2005
Actual Study Completion Date : March 2007

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 1
zoledronic acid plus radiation therapy
Drug: zoledronic acid
At baseline 4 mg IV zoledronic acid over 15 min. every 4 weeks for 6 months plus radiation therapy 30 Gy in 10 fractions (5 times per week for first two weeks)

Primary Outcome Measures :
  1. PET-CT [ Time Frame: baseline and 6 months ]

Secondary Outcome Measures :
  1. X-ray, baseline [ Time Frame: 3 months, 6 months ]
  2. physical exam [ Time Frame: Radiaton Oncology - visits 1, 14, 17 ]
  3. physical exam [ Time Frame: Medical Oncology - visits 1, 13, 17 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • >18 years of age
  • biopsy proven breast, lung, and/or prostate cancer
  • boney metastases with an indication for radiation, either diagnosed radiologically or biopsy proven
  • Karnofsky Performance Status >60
  • Life expectancy of at least 6 months
  • Serum creatinine level ≤ 2.0 mg/dL and calculated creatinine clearance of > 60 mL/min
  • Leukocyte count ≥ 3500/mm3
  • Hemoglobulin > 11 g/dl
  • Platelets > 100,000 / mm3
  • Total bilirubin < 2.5 mg/dl

Exclusion Criteria:

  • pregnant and lactating women (breast and lung cancer)
  • hormonotherapy started less than 3 months prior to randomization (prostate cancer)
  • history of allergic reactions to bisphosphonates
  • receiving concomitant nephrotoxic chemotherapy
  • participation in another clinical trial with an investigational drug or completed an investigational drug trial within the past 30 days
  • liver function tests > 1.5 times normal values
  • IV calcitonin administration less than 30 days prior to randomization
  • laboratory evidence of renal disease
  • previous RT to the region of bone metastasis which will be treated in this study
  • currently receiving oral or IV bisphosphonate therapy
  • presence of ascites
  • clinically significant electrocardiographic changes
  • hypercalcemia, pathologic fracture, or epidural spinal cord compression
  • other organ metastasis
  • known hypersensitivity to Zometa® (zoledronic acid) or other bisphosphonates
  • current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures.
  • recent (within 6 weeks) or planned dental or jaw surgery (e.g.. extraction, implants)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00264420

Sponsors and Collaborators
The Cleveland Clinic
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Principal Investigator: Roger Macklis, MD The Cleveland Clinic
Major RJ, Chen BL, et al. Multiple event analysis of zoledronic acid trials in patients with cancer metastatic to bone. Proc Am Soc Clin Oncol 22:762, 2003

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Responsible Party: Dawn Miller, Program Coordinator, Cleveland Clinic Foundation
ClinicalTrials.gov Identifier: NCT00264420    
Other Study ID Numbers: IRB7743
Case 8Y04
First Posted: December 12, 2005    Key Record Dates
Last Update Posted: December 21, 2010
Last Verified: December 2010
Keywords provided by The Cleveland Clinic:
bone metastases
breast cancer
lung cancer
prostate cancer
zoledronic acid
radiation therapy
Additional relevant MeSH terms:
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Breast Neoplasms
Lung Neoplasms
Prostatic Neoplasms
Neoplasm Metastasis
Bone Neoplasms
Bone Marrow Diseases
Neoplasms by Site
Breast Diseases
Skin Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Genital Neoplasms, Male
Urogenital Neoplasms
Prostatic Diseases
Neoplastic Processes
Pathologic Processes
Bone Diseases
Musculoskeletal Diseases
Hematologic Diseases
Zoledronic Acid
Bone Density Conservation Agents
Physiological Effects of Drugs